Work is in progress on characterizing the maturation of thymus-derived lymphocyte (T cell) precursors. These cells originate in the bone marrow and undergo some maturation in that site. At a critical stage they leave the marrow and enter the thymus, where they are triggered into a burst of proliferation and differentiation. Sufficiently differentiated (i.e., mature) T cells are exported from the thymus to become part of the functional immune system. We have developed an assay for T cell precursors, and have used it to study the factors which control production of these cells. A humoral factor made by the thymus controls levels of T cell precursors in the bone marrow. Thus a feed-back loop has been identified for the thymus, which may operate the way red cell mass feeds back on erythropoiesis. We will characterize the humoral factor and its target cell, and try to establish the mechanism by which it induces the first stages of maturation. Furthermore, we will characterize T cell precursors, before and after contact with the humoral factor, for T cell function (help, suppression, allogeneic recognition) and for two putative pre-T cell markers: terminal deoxynucleotidyl transferase, and natural killer activity.